The pathomechanisms which determine the brain's hemodynamic and metabolic recovery from periods of global cerebral ischemia will be studied in cats subjected to standardized ischemic insults. High-grade cerebral ischemia will be produced by occlusion of the basilar and both common carotid arteries and mild hemorrhagic hypotension, resulting in an isoelectric electroencephalogram. This insult will be compared with less severe ischemia produced by vascular occlusion with less hypotension, which permits residual EEG activity. The dependence of impaired post-ischemic microvascular reperfusion upon an antecedent stasis of brain blood flow will be investigated by comparing the above animal groups with animals subjected to mixed hypoxic-ischemia insult in which stasis does not occur. The 14C-iodoantipyrine autoradiographic method of local cerebral blood flow will be used to document inhomogeneous perfusion in the post-ischemic brain. In other brains, regional energy metabolites (phosphocreatine, adenosine, triphoshate (ATP), and lactate) will be assayed and correlated with regional cerebral blood flow determined in the same samples by radioactive microspheres; regional brain water content will be simultaneously determined by density gradient column. 14C-2-deoxyglucose will be employed as a secondary metabolic probe in selected animals to define the topography of the metabolic abnormalities occurring following ischemia. The effects of hyperglycemia and hypoglycemia upon post-ischemic brain perfusion and metabolism will be studied with the above methods. This investigation will serve to define the limits of the brain's tolerance to widespread ischemia such as may occur clinically during cardiac arrest or profound hypotension, and will clarify the metabolic and hemodynamic events underlying post-ischemic recovery of brain function.